Synthesis of hydantoin analogues of (2S,3R,4S)-4-hydroxyisoleucine with insulinotropic properties. Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] Journal article | | Title | Synthesis of hydantoin analogues of (2S,3R,4S)-4-hydroxyisoleucine with insulinotropic properties. | | Author(s) | Sergent D, Wang Q, Sasaki NA, Ouazzani J | | Institution | Institut de Chimie des Substances Naturelles, CNRS, UPR 2301, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. | | Source | Bioorg Med Chem Lett 2008 Jun 28. | | Abstract | The first synthesis of an optically pure (2R,3R,4S)-hydantoin 2, analogue of (2S,3R,4S)-4-hydroxyisoleucine, was achieved in two steps in un-optimized 35% overall yield from previously reported aldehyde synthon 1. (2R,3R,4S)-Hydantoin is stable at acidic pH. This solves the major drawback of (2S,3R,4S)-4-hydroxyisoleucine that easily cyclizes into inactive lactone. Furthermore, (2R,3R,4S)-hydantoin stimulates the insulin secretion by 150% at 25muM compared with 4-hydroxyisoleucine and insulin secretagogue drug repaglinide. In view of its stability and biological activity, (2R,3R,4S)-hydantoin represents a good candidate for type-2 diabetes management and control. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18621529 |
|
|
| |
Advertise on this site.
| | |
|
